There is a growing body of information consistent with the idea that there is an important interrelationship between the metabolism of leucine and ketone bodies. This involves not only a direct formation of ketone bodies from leucine, but possibly also some effect on the regulation of proteolysis in muscle. It is the present consensus that the quantitative significance of the conversion of leucine to ketone bodies is insignificant because it is believed that ketone bodies arise almost entirely from fatty acid carbon. It is for this reason that all attempts to determine the mechanism of ketone body production have centered on fatty acid metabolism. We have obtained in vivo data in starved rats showing that one third of ketone body carbon is derived from a source(s) other than fatty acids. Preliminary data indicates that leucine may be the major component of this missing carbon source. If this can be documented, it would introduce a new dimension into the search for the mechanism of regulation of ketogenesis. In this project, I propose to quantify the fraction of ketone body carbon derived from leucine. In addition, I propose to examine how the relative contributions of these different carbon sources vary when the nutritional status of the animals is altered. This should provide a more detailed understanding of the process of ketogenesis and of the role played by leucine in vivo.